title: Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations.
abstract: OBJECTIVE
  Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed.
  
  
  METHODS
  Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time.
  
  
  RESULTS
  Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P = .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P < .001) and dyspnea (P < .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P < .001), role (P = .004), and cognitive (P = .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P < .01).
  
  
  CONCLUSIONS
  In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.
authors.affiliation: James Chih-Hsin Yang, National Taiwan University Hospital, Taipei, Taiwan; Vera Hirsh, McGill University, Montreal, Quebec, Canada; Martin Schuler, West German Cancer Center, University Duisburg-Essen, Essen; Juliane Lungershausen, Boehringer Ingelheim GmbH, Ingelheim, Germany; Nobuyuki Yamamoto, Shizuoka Cancer Center, Shizuoka, Japan; Kenneth J. O'Byrne, St James' Hospital, Dublin, Ireland; Tony S.K. Mok, State Key Laboratory of Southern China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Hong Kong; Victoria Zazulina, Mehdi Shahidi, and Dan Massey, Boehringer Ingelheim Limited, Bracknell; Michael Palmer, Keele University, Keele, United Kingdom; and Lecia V. Sequist, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.forename: Vera
authors.initials: V
authors.lastname: Hirsh
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: Tony S K
authors.initials: TS
authors.lastname: Mok
authors.forename: Victoria
authors.initials: V
authors.lastname: Zazulina
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shahidi
authors.forename: Juliane
authors.initials: J
authors.lastname: Lungershausen
authors.forename: Dan
authors.initials: D
authors.lastname: Massey
authors.forename: Michael
authors.initials: M
authors.lastname: Palmer
authors.forename: Lecia V
authors.initials: LV
authors.lastname: Sequist
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077716:Afatinib; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D066246:ErbB Receptors / Q000235:genetics*; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D000077716:Afatinib; D006147:Guanine; D066246:ErbB Receptors; D002945:Cisplatin